Mosaic Trisomies 8, 9, and 16

Introduction

Trisomies can occur with any chromosome, but most often result in spontaneous abortion. For example, trisomy 16 is the most common trisomy in human pregnancies, and the majority of the time results in miscarriage. These severe trisomies are more likely to survive past the first trimester and possibly to birth if they are mosaics, in which the condition of trisomy only affects a portion of the cells in the body. Here, we discuss mosaic trisomies 8, 9, and 16.

Disorder

Trisomy 8

Definition

Trisomy 8 mosaicism is a genetic abnormality that results from a cell line with an extra chromosome number 8 in addition to a genetically normal cell line. Trisomy 8 mosaicism is also called Warkany syndrome 2. Unlike some other trisomies, trisomy 8 mosaicism can be compatible with life. These individuals vary in phenotype and can be recognized by mental retardation, abnormal facies, absent or dysplastic patellas, joint contractures, plantar/palmar furrows, distinctively abnormal toe posture, vertebral anomalies, narrow pelvis, and urorenal anomalies. ²

Prevalence and Epidemiology

Mosaic trisomy 8 is estimated in 2–4 : 100,000 births. Eight of 10 spontaneous abortions is due to complete trisomy 8, which is lethal in a conceptus. There is a 3 : 1 male-to-female sex ratio in the mosaic cases. ³ A review of PubMed's database shows that only 120 cases have been reported.

Etiology and Pathophysiology

According to Fineman et al., chromosome 8 is the “largest autosome thus far found to be trisomic among live-born infants.” Most cases of trisomy 8 mosaicism result from mitotic nondisjunction.

Manifestations of Disease

Clinical Presentation

Mosaic trisomy 8 has a wide range of clinical phenotypes depending on the cell lines present. Individuals can be normal or have severe malformations. Twenty-five per cent of patients may have congenital cardiac malformations. Other physical findings of live-born infants with trisomy 8 mosaicism include mild-to-moderate mental retardation due to corpus callosum agenesis, strabismus, osseous and soft tissue abnormalities, broad bulbous nose, palate deformity, hydronephrosis, cryptorchidism, reduced joint mobility, various vertebral and costal anomalies, eye anomalies, camptodactyly, and deep plantar and palmar creases. Deep plantar creases are very characteristic of this disease.

Imaging Technique and Findings

Ultrasound.

Ultrasound (US) can identify cases of suspected trisomy 8 mosaicism. US findings include agenesis of the corpus callosum, hydrocephalus, abnormal facies, cardiac malformations, ventriculomegaly, and joint contractures.

Magnetic Resonance Imaging.

There are few cases that address magnetic resonance imaging (MRI) in trisomy 8 mosaicism. However, MRI can further characterize brain abnormalities, including enlarged lateral ventricles and corpus callosum agenesis, which exist in trisomy 8 mosaicism. One case report describes a 33-year-old man treated for Marfan syndrome during childhood who presented with “lumbar spine herniated nucleus propulsus” on MRI.

Differential Diagnosis From Imaging Findings

1.
Other trisomies
2.
Syndromes with Arthrogryposis

Other trisomies should be on the differential diagnosis for trisomy 8 mosaicism. Syndromes with arthrogryposis should be differentiated from trisomy 8 mosaicism. Both diagnoses include joint contractures. Arthrogryposis syndromes are multifactorial and it is often hard to find a cause.

Synopsis of Treatment Options

Prenatal

Most patients with mosaic trisomy 8 will be detected with chorionic villus sampling; however, the results are not specific. This is due to the fact that trisomy 8 mosaic found in the sample may be due to confined placental mosaicism. Like other chromosomal abnormalities, maternal serum alpha-fetoprotein (MSAFP) may be in trisomy 8 mosaicism. Amniocentesis can confirm the diagnosis.

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